Despite advances in the understanding of age-related changes in cognition, there is still a need to unravel the biological mechanisms underlying normal cognitive aging, which has important financial and public health implications for society. Cognitive aging is not dementia and does not result in the loss of neurons, but rather changes in neurotransmission that affect brain functioning. Therefore, there is potential for remediation. Observational studies suggest that following a diet that is high in the monounsaturated fatty acid (FA), oleic acid (OA), and low in the saturated FA, palmitic acid (PA), lowers the rate of cognitive decline with aging, but these studies do not primarily assess mechanism. The study proposed in this application will determine whether and how dietary PA and OA alter brain functioning. Data from this laboratory showed that a high dietary PA/OA ratio, in a reversible fashion, enhanced systemic inflammatory tone, affected activation of brain regions that regulate cognition, and decreased physical activity in younger adults. In addition, the literature suggests that dietary PA will reduce sleep efficiency as well as brain expression of brain-derived neurotrophic factor (BDNF). The objective of this proposal is to test the hypothesis that lowering the dietary PA/OA ratio will decrease inflammatory signaling and will lead to better memory performance and increased hippocampal activation during an episodic memory task. To evaluate this hypothesis, a randomized, double-masked, cross-over trial in healthy, older adults, aged 65-75 years is proposed. Each subject will receive, in random order either a high PA diet (HPA) or a low PA, high OA diet (HOA), each for a duration of three weeks and each preceded by a one week, low-fat control diet. Specific Aim 1 is to determine if dietary PA and OA differentially and reversibly affect brain functioning in older adults. Hypothesis 1a is that the HOA diet compared to the HPA diet will result in improved episodic memory performance in older adults. Hypothesis 1b is that the HOA diet compared to the HPA diet will result in increased hippocampal activation during episodic memory encoding in older adults during fMRI. Specific Aim 2 is to determine if pro-inflammatory cytokines and blood concentrations of BDNF are related to dietary FA-induced changes in brain functioning in older adults. Hypothesis 2 is that decreased inflammation after the HOA diet, compared to the HPA diet, will be associated with improved episodic memory performance, hippocampal brain activation, and increased blood concentration of BDNF. In addition, we will conduct exploratory studies to determine if the following factors modify this relationship: physical activity, sleep efficiency, emotional stress, and both percent body fat and plasma leptin concentration at baseline. The results of this study will impact the understanding of how short-term changes in the dietary PA/OA ratio reversibly influence brain functioning in older adults, providing a novel basis for linking diet to dynamic variations in inflammatory activity and cognitive functioning that occur with normal aging.